scholarly journals Therapeutic Efficacy of Nyctanthes arbor-tristis Flowers to Inhibit Proliferation of Acute and Chronic Primary Human Leukemia Cells, with Adipocyte Differentiation and in Silico Analysis of Interactions between Survivin Protein and Selected Secondary Metabolites

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 165 ◽  
Author(s):  
Saumya Nishanga Heendeniya ◽  
Lakshika. Rangi Keerthirathna ◽  
Chamalika Kanthini Manawadu ◽  
Indeewarie Hemamali Dissanayake ◽  
Rizwan Ali ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Glucose Uptake ◽  
High Specific Activity ◽  
Lymphocytic Leukemia ◽  
Yeast Cells ◽  
Mass Spectrometry Analysis ◽  
Hexane Fraction ◽  
Human Leukemia ◽  
Dependent Manner ◽  
Survivin Protein

Although the antidiabetic efficacy of Nyctanthes arbor-tristis flowers has been reported, antiproliferative and anti-obesity activities are yet to be explored. We examined the anti-obesity and antiproliferative potentials of different fractions (hexane, chloroform, ethyl acetate, methanol) of N. abor-tristis flower extract for the first time using 3T3-L1 cells, primary peripheral blood mononuclear cells (PBMC) isolated from healthy and adult acute myeloid (AML) and chronic lymphocytic leukemia (CLL) patients, recombinant Jurkat T cells, and MCF7 cell lines. The in vitro hypoglycemic activity was evaluated using the inhibition of α-amylase enzyme and glucose uptake by yeast cells. The percentage glucose uptake and α-amylase inhibitory activity increased in a dose-dependent manner in the crude and the tested fractions (hexane and ethyl acetate). Inhibition of the 3T3-L1 cells’ differentiation was observed in the ethyl acetate and chloroform fractions, followed by the hexane fraction. Antiproliferative analyses revealed that Nyctanthes exerted a high specific activity against anti-AML and anti-CLL PBMC cells, especially by the hexane and ethyl acetate fractions. The gas chromatography/mass spectrometry analysis indicated the presence of 1-heptacosanol (hexane fraction), 1-octadecene (hexane and chloroform fractions), and other organic compounds. Molecular docking demonstrated that phenol,2,5-bis(1,1-dimethylethyl) and 4-hydroxypyridine 1-oxide compounds showed specificity toward survivin protein, indicating the feasibility of N. abor-tristis in developing new drug leads against leukemia.

Comparative free radical scavenging and hypoglycemic activities of n-hexane, ethyl-acetate, and aqueous fractions of Azanza garckeana pulp

2021 ◽  
Vol 1 (2) ◽  
pp. 1-8
Author(s):  
Abubakar A. Yusuf ◽  
Toheeb D. Yissa ◽  
Abdulhakeem Rotimi Agboola ◽  
Sodiq M Balogun ◽  
Peter O. Adeboye ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Radical Scavenging ◽  
Ethyl Acetate Fraction ◽  
Diabetic Rats ◽  
Hypoglycemic Effect ◽  
Hexane Fraction ◽  
Dependent Manner ◽  
Aqueous Fraction ◽  
Dpph Scavenging ◽  
Glucose Reduction

Background: The prevalence of diabetes mellitus is increasing on a global trend. The aim of the present study is to identify the most effective antioxidants and hypoglycemic fraction of Azanza garckeana. Methods: The fractions (nhexane or ethyl-acetate or aqueous) of A. garckeana were administered to the alloxan-induced diabetic rats at doses of 100, 200, and 400 mg/kg for 15 days. Antioxidants activities were evaluated at concentrations of 62.5, 125, 250, and 500 µg/mL using the DPPH scavenging assay. Results: Results revealed that both the hexane, ethyl-acetate, and aqueous fractions exhibited hypoglycemic and antioxidants activities in a dose-dependent manner. The n-hexane fraction demonstrated highest percentage DPPH scavenging effect of 26.34±3.43, 38.44±4.35, 59.34±3.45, and 74.83±5.35 at 62.5, 125, 250, and 500 µg/mL respectively. The ethyl-acetate fraction demonstrated 19.33±2.98, 28.94±3.24, 47.34±2.90, and 57.82±4.54 respectively while the aqueous fraction exhibited the least activities of 12.45±23.45, 18.64±2.94, 27.94±3.89, and 39.43±3.89 at concentrations of 62.5, 125, 250, and 500 µg/mL respectively. In addition, the n-hexane fraction demonstrated the most significant hypoglycemic effect with the highest glucose reduction of 58.97 ±3.45 %, 63.86±5.35 %, and 66.51±4.35 %, ethyl acetate fraction demonstrated glucose reduction of 7.55±0.54%, 21.77±2.35 %, and 29.56±3.46 % while the aqueous fraction demonstrated the least hypoglycemic effect of 9.89±2.67 %, 18.09±3.45 %, and 18.87±3.24 at 100, 200 and 400 mg/kg bw respectively. Conclusion: The n-hexane fraction of Azanza garckeana extract could serve as a reservoir of bioactive agents that could be useful for the development of a new anti-diabetic agent

scholarly journals In vitro antidiabetic, anti-inflammatory and antioxidant potential of the ethanol extract of Uromastyx hardwickii skin

2021 ◽  
Vol 18 (10) ◽  
pp. 2109-2115
Author(s):  
Waqas Ahmad Shams ◽  
Gauhar Rehman ◽  
Samuel Okwudili Onoja ◽  
Abid Ali ◽  
Khurshaid Khan ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Glucose Uptake ◽  
Ethanol Extract ◽  
Antioxidant Potential ◽  
Yeast Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anti Inflammatory

Purpose: To evaluate the in vitro antidiabetic, anti-inflammatory and antioxidant potential of the ethanol extract of Uromastyx hardwickii Skin (UHSEE). Methods: The in vitro effects of UHSEE at various concentrations (10 - 250 µg/mL) on the activities of ߙ-amylase, ߙ-glucosidase and glucose uptake by yeast cells were used to evaluate its antidiabetic potential. Nitric oxide (NO), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide inhibitory assay were employed to determine its antioxidant effects, while the anti-inflammatory effects were evaluated using human red blood cell (HRBC) membrane stabilization assay. Results: UHSEE inhibited ߙ-amylase and ߙ-glucosidase enzymes but increased glucose uptake by yeast cells in a concentration-dependent manner (p < 0.05). It also inhibited NO, DPPH, hydrogen peroxide and HRBC hemolysis in a concentration-dependent manner (p < 0.05). Conclusion: Uromastyx hardwickii skin exhibits promising good antidiabetic, antioxidant and antiinflammatory properties in vitro. However, its true potentials in this regard needs to be evaluted in vivo.

scholarly journals Extract of white sweet potato tuber against TNF-α-induced insulin resistance by activating the PI3K/Akt pathway in C2C12 myotubes

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lie-Fen Shyur ◽  
Viola Varga ◽  
Chiao-Ming Chen ◽  
Shu-Chi Mu ◽  
Yu-Chih Chang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ethyl Acetate ◽  
Glucose Uptake ◽  
Sweet Potato ◽  
Akt Pathway ◽  
C2c12 Myotubes ◽  
Total Phenolic ◽  
C2c12 Myoblast ◽  
Dependent Manner ◽  
Tnf Α

Abstract Background White sweet potato (WSP; Ipomoea batatas L. Simon No. 1) has many potential beneficial effects on metabolic control and diabetes-related insulin resistance. The improvement of insulin resistance by WSP tuber extracts on glucose uptake were not investigated in C2C12 myoblast cells. Results WSP tuberous ethanol extract (WSP-E) was partitioned with ethyl-acetate and water to obtain ethyl-acetate layer (WSP-EA) and water layer (WSP-EW). The WSP-EA shows the highest total phenolic contents and highest antioxidant activity by Folin-Ciocalteu and (2,2-diphenyl-1-picryl-hydrazyl-hydrate, DPPH) assay, respectively. After low concentration horse serum on differentiation inducement of C2C12 myoblasts into mature myotubes, the cells were treated with TNF-α to induce insulin resistance. WSP-EA and WSP-EW extracts increased the uptake of fluorescence glucose analogue (2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-d-glucose, 2-NBDG) in a dose-dependent manner as examined by flow cytometry. The WSP-EA enhanced glucose uptake by activation of phosphorylation of IR (pIR), IRS-1 (pIRS-1) and Akt (pAkt) involved in PI3K (phosphatidylinositol 3-kinase)/protein kinase B (Akt) pathway, also upregulated glucose transporter 4 (GLUT4) expression in myotubes. Conclusions WSP-EA enhanced the glucose uptake in C2C12 myotubes through upregulating the PI3K/Akt pathway. The in vitro data reveal that WSP tuber extracts has potential applications to improve insulin resistance in diabetes.

scholarly journals Evaluation of in vitro antioxidant, antidiabetic activities and GC-MS analysis from Amomum nilgiricum leaf extract

2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Narasimhamurthy Konappa ◽  
Udayashankar C Arakere ◽  
Soumya Krishnamurthy ◽  
Kusuma Chathrapalya Gangadharaiah ◽  
Vinod Gubbiveeranna ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Ethyl Acetate Fraction ◽  
Yeast Cells ◽  
Mass Spectrometry Analysis ◽  
Antidiabetic Activity ◽  
Gas Chromatography Mass Spectrometry ◽  
Methanol Fraction ◽  
Ms Analysis ◽  
Ic50 Value

In the present study, hexane, ethyl acetate and methanol fraction of Amomum nilgiricum leaf was evaluated for antidiabetic efficacy through in vitro ?-amylase and ?-glucosidase assays, DPPH and H2O2 scavenging activities, followed by estimation of total phenol, total flavonoids and gas chromatography-mass spectrometry analysis. In the present study, a significant amounts of total phenolics (79.92±1.58 mg/g) and flavonoids (21.74± 0.89 mg/g) were showed from Ethyl acetae faction. Ethyl acetate fraction showed maximum inhibition of DPPH radicals (82.31±2.33%) with IC50 value of 52 µg/ml and H2O2 scavenging activity (97.62±2.89%) with IC50 value of 78.57 µg/ml concentrations. The ethyl acetate fraction was revealed maximum ?-amylase inhibition (77.23± 3.21%) with IC50 value 76.53 µg/ml. The ethyl acetate fraction recorded maximum ?-glucosidase inhibition (85.36±2.58%) with IC50 value 79.54 µg/ml. Ethyl acetate fraction exhibited maximum inhibitory activity of glucose movement into outer solution across dialysis membrane at 250 µg/ml as compared to the control. The ethyl acetate fraction revealed maximum insulin secretory activity (130.5±3.66%) in RIN-m5F cells. Methanol fraction recorded maximum glucose uptake percent in yeast cells (67.08±1.68%) when compared to standard metronidazole (68.06±0.73%). The GC-MS analysis of ethyl acetate fraction was recorded the presence of six phytochemical constituents. This study scientifically validates the antidiabetic activity of A. nilgiricum. Hence, in view of its comparative hypoglycemic strength, it can work as a valuable healing agent in treating diabetes.

Antioxidant and Anti-inflammatory Activities of Organic and Aqueous Extracts of Northeast Algerian Marrubium vulgare

2018 ◽  
Vol 16 (S1) ◽  
pp. S119-S129
Author(s):  
I. Namoune ◽  
B. Khettal ◽  
A.M. Assaf ◽  
S. Elhayek ◽  
L. Arrar
Keyword(s):  
Ethyl Acetate ◽  
Methanolic Extract ◽  
Ethyl Acetate Extract ◽  
Interleukin 1 ◽  
Total Phenolic ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Traditional Use ◽  
Marrubium Vulgare ◽  
Anti Inflammatory

Marrubium vulgare (Lamiaceae) is frequently used in traditional medicine to treat many illnesses from ancient times. Its beneficial effects include antibacterial, antioedematogenic, and analgesic activities. This study was designed to evaluate the antioxidant and anti-inflammatory activities of organic and aqueous extracts of the leaves, the flowers, the stems, and the roots of Marrubium vulgare. The total phenolic and flavonoid contents as well as the antioxidant and the anti-inflammatory effects of methanol, chloroform, ethyl acetate, and aqueous extracts have been investigated by using different in-vitro methods. It was found that the ethyl acetate extract from Marrubium vulgare stems had the highest total phenolic content, while the ethyl acetate extract from the leaves yielded a high concentration of flavonoids. The ethyl acetate extract from the stems exhibited the highest activity in scavenging of 2,2-diphenyl- 1-picrylhydrazyl (DPPH), as well as in protecting erythrocytes. The leaves aqueous extract exhibited the highest ferrous chelating activity and its methanolic extract was found to be the strongest inhibitor of lipid peroxidation in β-carotene bleaching assay. The leaves chloroform extracts as well as the flowers methanol, chloroform, and ethyl acetate extracts were found to decrease the pro-inflammatory tumor necrosis factor alpha (TNF-α) cytokine levels in a dose-dependent manner. On the other hand, the flowers methanolic extract and the leaves methanol, ethyl acetate, and aqueous extracts decreased the interleukin-1 beta (IL- 1β) release. It was also found that the methanol extract from the flowers and the chloroform extract from the stems of Marrubium vulgare inhibited interleukin-8 (IL-8) release. This study provides a scientific basis for the traditional use of Marrubium vulgare as an anti-inflammatory agent and for the plant to be considered as an important resource of natural antioxidants.

Phytochemical Investigation and Antimutagenic Potential of Ethanolic Extracts of Emblica officinalis, Terminalia chebula and Terminalia bellirica

2020 ◽  
Vol 10 (4) ◽  
pp. 488-494 ◽  
Author(s):  
Venugopal Singamaneni ◽  
Sudheer Kumar Dokuparthi ◽  
Nilanjana Banerjee ◽  
Ashish Kumar ◽  
Tulika Chakrabarti
Keyword(s):  
Ethyl Acetate ◽  
Gallic Acid ◽  
Ellagic Acid ◽  
Antimutagenic Activity ◽  
Dependent Manner ◽  
Terminalia Chebula ◽  
Emblica Officinalis ◽  
Dried Fruits ◽  
Terminalia Bellerica ◽  
The Family

Background: Emblica officinalis Gaertn. which belongs to the family Euphorbiaceae, Terminalia chebula Retz. and Terminalia bellerica Roxb. belong to the family Combretaceae. These are well known medicinal plants with phytochemical reservoir of great medicinal values and possess a vast ethnomedical history. Objective: The aim of the present study is to isolation of major compounds and to evaluate antimutagenic potential of the ethanol extracts of these plants. Methods: The dried fruits of E. officinalis, T. bellirica and T. chebula were powdered and extracted with 95% ethanol. The ethyl acetate portions were chromatographed over silica gel to isolate major compounds. Antimutagenic activity was determined by Ames test using TA98 and TA100 strains of Salmonella typhimurium. Results: Two major known compounds, gallic acid and ellagic acid were isolated from the dried fruits of Emblica officinalis, Terminalia chebula and T. bellirica. All the three extracts counteracted the mutagenicity induced by different genotoxic compounds in a dose dependent manner. Conclusion: This study showed that ethyl acetate portion of three extracts contain two major compounds, gallic acid and ellagic acid which might be responsible for potent antimutagenic activity of these extracts.

scholarly journals Phytochemicals of Minthostachys diffusa Epling and Their Health-Promoting Bioactivities

Foods ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 144
Author(s):  
Immacolata Faraone ◽  
Daniela Russo ◽  
Lucia Chiummiento ◽  
Eloy Fernandez ◽  
Alka Choudhary ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Radical Scavenging ◽  
Ethyl Acetate Fraction ◽  
Mass Spectrometry Analysis ◽  
Antioxidant Power ◽  
Spectrometry Analysis ◽  
In Silico Docking ◽  
Aerial Parts ◽  
Health Promoting

The genus Minthostachys belonging to the Lamiaceae family, and is an important South American mint genus used commonly in folk medicine as an aroma in cooking. The phytochemical-rich samples of the aerial parts of Minthostachys diffusa Epling. were tested for pharmacological and health-promoting bioactivities using in vitro chemical and enzymatic assays. A range of radical scavenging activities of the samples against biological radicals such as nitric oxide and superoxide anion and against synthetic 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals, the ferric reducing antioxidant power and the lipid peroxidation inhibition were determined and ranked using the ‘relative antioxidant capacity index’ (RACI). The ethyl acetate fraction showed the highest RACI of +1.12. Analysis of the various fractions’ inhibitory ability against enzymes involved in diabetes (α-amylase and α-glucosidase), and against enzymes associated with Parkinson’s or Alzheimer’s diseases (acetylcholinesterase and butyrylcholinesterase) also suggested that the ethyl acetate fraction was the most active. Liquid chromatography–tandem mass spectrometry analysis of the ethyl acetate fraction showed more than 30 polyphenolic compounds, including triterpenes. The inhibitory cholinesterase effects of the triterpenes identified from M. diffusa were further analysed by in silico docking of these compounds into 3D-structures of acetylcholinesterase and butyrylcholinesterase. This is the first study on pharmacological activities and phytochemical profiling of the aerial parts of M. diffusa, showing that this plant, normally used as food in South America, is also rich in health-promoting phytochemicals.

scholarly journals Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses

2020 ◽  
Vol 4 (10) ◽  
pp. 2143-2157 ◽  
Author(s):  
Alak Manna ◽  
Timothy Kellett ◽  
Sonikpreet Aulakh ◽  
Laura J. Lewis-Tuffin ◽  
Navnita Dutta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Dependent Manner

Abstract Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.

scholarly journals Relation of Gene Expression Phenotype to Immunoglobulin Mutation Genotype in B Cell Chronic Lymphocytic Leukemia

2001 ◽  
Vol 194 (11) ◽  
pp. 1639-1648 ◽  
Author(s):  
Andreas Rosenwald ◽  
Ash A. Alizadeh ◽  
George Widhopf ◽  
Richard Simon ◽  
R. Eric Davis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Germ Line ◽  
Gene Expression Signature ◽  
Lymphocytic Leukemia ◽  
Common Mechanism ◽  
Human Leukemia ◽  
Mutational Status ◽  
Cell Chronic Lymphocytic Leukemia

The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression “signature,” irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.

scholarly journals Low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for apolipoprotein A4 (APOA4) in adipose tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Qu ◽  
Sarah Fourman ◽  
Maureen Fitzgerald ◽  
Min Liu ◽  
Supna Nair ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Receptor ◽  
Dependent Manner ◽  
Related Protein ◽  
Density Lipoprotein Receptor ◽  
Lipoprotein Receptor Related Protein

AbstractApolipoprotein A4 (APOA4) is one of the most abundant and versatile apolipoproteins facilitating lipid transport and metabolism. APOA4 is synthesized in the small intestine, packaged onto chylomicrons, secreted into intestinal lymph and transported via circulation to several tissues, including adipose. Since its discovery nearly 4 decades ago, to date, only platelet integrin αIIbβ3 has been identified as APOA4 receptor in the plasma. Using co-immunoprecipitation coupled with mass spectrometry, we probed the APOA4 interactome in mouse gonadal fat tissue, where ApoA4 gene is not transcribed but APOA4 protein is abundant. We demonstrate that lipoprotein receptor-related protein 1 (LRP1) is the cognate receptor for APOA4 in adipose tissue. LRP1 colocalized with APOA4 in adipocytes; it interacted with APOA4 under fasting condition and their interaction was enhanced during lipid feeding concomitant with increased APOA4 levels in plasma. In 3T3-L1 mature adipocytes, APOA4 promoted glucose uptake both in absence and presence of insulin in a dose-dependent manner. Knockdown of LRP1 abrogated APOA4-induced glucose uptake as well as activation of phosphatidylinositol 3 kinase (PI3K)-mediated protein kinase B (AKT). Taken together, we identified LRP1 as a novel receptor for APOA4 in promoting glucose uptake. Considering both APOA4 and LRP1 are multifunctional players in lipid and glucose metabolism, our finding opens up a door to better understand the molecular mechanisms along APOA4-LRP1 axis, whose dysregulation leads to obesity, cardiovascular disease, and diabetes.

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